Chronic temporal lobe epilepsy: a neurodevelopmental or progressively dementing disease?

Abstract

To what degree does the so-called 'initial hit' of the brain versus chronic epilepsy contribute towards the memory impairment observed in chronic temporal lobe epilepsy (TLE) patients? We examined cross-sectional comparisons of age-related regressions of verbal learning and memory in 1156 patients with chronic TLE (age range 6-68 years, mean epilepsy onset 14 +/- 11 years) versus 1000 healthy control subjects (age range 6-80 years) and tested the hypothesis that deviations of age regressions (i.e. slowed rise, accelerated decline) will reveal critical phases during which epilepsy interferes with cognitive development. Patients were recruited over a 20-year period at the Department of Epileptology, University of Bonn. Healthy subjects were drawn from an updated normative population of the Verbaler Lern- und Merkfähigkeitstest, the German pendant to the Rey Auditory Verbal learning Test. A significant divergence of age regressions indicates that patients fail to build up adequate learning and memory performance during childhood and particularly during adolescence. The learning peak (i.e. crossover into decline) is seen earlier in patients (at about the age of 16-17 years) than for controls (at about the age of 23-24 years). Decline in performance with ageing in patients and controls runs in parallel, but due to the initial distance between the groups, patients reach very poor performance levels much earlier than controls. Patients with left and right TLEs performed worse in verbal memory than controls. In addition, patients with left TLE performed worse than those with right TLE. However, laterality differences were evident only in adolescent and adult patients, and not (or less so) in children and older patients. Independent of age, hippocampal sclerosis was associated with poorer performance than other pathologies. The results indicate developmental hindrance plus a negative interaction of cognitive impairment with mental ageing, rather than a progressively dementing decline in chronic TLE patients. During childhood, and even more so during the decade following puberty, the critical phases for establishing episodic memory deficits appear. This increases the risk of premature 'dementia' later on, even in the absence of an accelerated decline. Material specific verbal memory impairment in left TLE is a characteristic of the mature brain and seems to disappear at an older age. The findings suggest that increased attention is to be paid to the time of epilepsy onset and thereafter. Early control of epilepsy is demanded to counteract developmental hindrance and damage at a younger age.

Five-Year Neuropsychological Outcome after Stereotactic Radiofrequency Amygdalohippocampectomy for Mesial Temporal Lobe Epilepsy: Longitudinal Study

“…Verbal memory deficit is the most frequently reported dysfunction, especially in patients with dominant MTLE. It is debatable whether or not this is a consequence of the initial precipitating injury, ongoing seizures, or structural pathology [28]. After an epilepsy surgery, these patients are at risk of further deterioration occurring in up to 30% [29].…”

Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy

“…Likewise, we cannot be certain that our model mimics severe ongoing poorly controlled epilepsy, in addition to being a model largely of the consequences of status epilepticus. However, there is strong clinical evidence that cognitive deficit in human mesial temporal lobe epilepsy is related to the degree of initial insult and not to the rate of spontaneous seizures (Helmstaedter and Elger, 2009). This is supported by longitudinal volumetric MRI studies, showing that brain volume reduction in temporal lobe epilepsy is the cumulative effect of an initial precipitating injury and age-related cerebral Figure 8 Fluoxetine (FLX) reverses the neurogenic deficit after kainate.…”

Autistic characteristics in adults with epilepsy

“…Evidence for the neurodevelopmental hypothesis originates from brain volumetric studies which show that early onset TLE has a negative effect on extratemporal cortical development (Kaaden & Helmstaedter, 2009). As chronic epilepsy patients often perform worse in cognitive assessments, Helmstaedter and Elger attempt to directly address the question of whether chronic TLE is a progressive disease, or whether there is a neuro-developmental hindrance (Helmstaedter & Elger, 2009). Their study indicates a developmental hindrance which suggests that TLE should not be regarded as a progressive disease, but that at its origin, epilepsy interferes with brain maturation and cognitive development (ibid.…”